Neuroscience, Live!

December 2, 2009 12:19 PM

HM was the subject of many landmark studies in neuroscience. After his hippocampus was removed to control epileptic seizures, he was unable to form long-term memories. University of California - San Diego's Brain Observatory is shaving his brain now, sliver after sliver, and posting the live camera feed on the web.

Why they're doing it, and what they hope to learn.

posted by Vhanudux (86 comments total)

Great--now I've got the jingle for that Tom Hanks SNL sketch, "Mr. Short Term Memory", going through my head. (Well, at least I don't have amnesia, anterograde or retrograde...)
posted by Halloween Jack at 12:23 PM on December 2, 2009

Needs more brains.
posted by sharpener at 12:29 PM on December 2, 2009 [1 favorite]

This is awesome. It's made even more awesome by the fact that the current operator is wearing a shirt, tie and vest, and sporting a nicely trimmed mustache and small goatee.

"Sure we're doing complex, amazing science here folks, but I've got to look my best. What if the Queen drops in for a look? I'll be damned if she's going to catch me in anything less than shirtsleeves and a tie!"
posted by Science! at 12:31 PM on December 2, 2009 [3 favorites]

Histology tech dude not only smartly dressed and groomed, but is hardcore--handling dry ice with his bare hands!
posted by Turtles all the way down at 12:34 PM on December 2, 2009

Have I ever told you about Sammy Jenkins?
posted by bfranklin at 12:36 PM on December 2, 2009 [5 favorites]

Right in my back yard! SD FTW!

OK, this is ridiculously cool. I'm gonna get my turkey sandwich and sit and watch for a while... Yay science!
posted by yiftach at 12:37 PM on December 2, 2009

I think I just saw the first cut?

And what is he using that paintbrush for?
posted by yiftach at 12:39 PM on December 2, 2009

Looks like they still haven't hit brains..they are 40 minutes behind schedule already.
posted by spicynuts at 12:40 PM on December 2, 2009

is shaving his brain now, sliver after sliver, and posting the live camera feed on the web

No way clicking on that link.
posted by stbalbach at 12:41 PM on December 2, 2009

It's not as graphic as it sounds, stbalbach.

Yet.
posted by yiftach at 12:43 PM on December 2, 2009

"Wow! Who knew that all we had to do was shave a brain on the webcam to get a buttload of hits!"
posted by markkraft at 12:45 PM on December 2, 2009

Who is the chick in the red blouse? She was all over Mr. Braincutter there, squeezing his arm, stroking his shoulder. Not a process that I would find romantic, personally, but there is no accounting for individual thrills.
posted by jeanmari at 12:48 PM on December 2, 2009

I guess it would've been helpful to post that HM died last year, and that he's not currently using the brain being shaved.
posted by Vhanudux at 12:51 PM on December 2, 2009 [21 favorites]

Oh, and by the way, the smartly dressed, coiffed and facial-hair-gifted microtome operator is not just a "histology tech dude" - it's Jacopo Annese, director of the UCSD Brain Observatory
posted by yiftach at 12:52 PM on December 2, 2009

Ah. The guy doing the honors at this point is Jacopo Annese.
posted by jeanmari at 12:53 PM on December 2, 2009

I was JUST coming here to post this! It's super awesome.
posted by gaspode at 12:53 PM on December 2, 2009

Oh, and previously, previously, previously.
posted by gaspode at 12:58 PM on December 2, 2009

At least they waited until no-shave-November was over.
posted by greensweater at 12:59 PM on December 2, 2009 [2 favorites]

Jinx, jeanmari! Actually, thanks for finding that bio. All I had was the pic in the news piece.
posted by yiftach at 1:01 PM on December 2, 2009

It's so great of his family to donate his body to neuroscience. The brain is such a mystery, and it must have been a really awful tragedy for his family.

It's strange how neuroscience tends to develop from all these problems. As my family has bipolar disorder and autism in our genes, I can't begin to say how grateful I am for the contributions from people like HM and his family.
posted by mccarty.tim at 1:01 PM on December 2, 2009

That sounds so amazingly cool! I am so not watching it!
posted by ardgedee at 1:16 PM on December 2, 2009

Gorgeous and fascinating. Thanks!
posted by fcummins at 1:19 PM on December 2, 2009

Man, scooped again. This is unstoppably awesome. There go my next 30 hours...
posted by solipsophistocracy at 1:23 PM on December 2, 2009

Who is the chick in the red blouse?

The woman in red is Dr. Natalie Schenker. pic, pic, pic. CV.

“There’s something mesmerizing about doing this,” said Natalie Schenker, a postdoctoral research associate as she dabbed and deposited slices of control brain. “It’s like going on a journey, each slice getting you to another place in the brain.”
posted by stavrogin at 1:30 PM on December 2, 2009 [1 favorite]

To those not watching it - you can't really SEE anything. They're shining a pretty bright light on the fixture material (likely so the poor guy can see what he's microtoming).
posted by muddgirl at 1:32 PM on December 2, 2009

It's making me really nervous when he's got a slice hanging from that paintbrush and he's having a fairly animated conversation at the same time. Stop waving your arms around!

I'm loving my alma mater right now.
posted by natabat at 1:35 PM on December 2, 2009

And what is he using that paintbrush for?
posted by yiftach at 3:39 PM on December 2 [+] [!]

You use the paintbrush bristles to pick up the slices, because tweezers can poke a hole in the tissue.
posted by NikitaNikita at 1:36 PM on December 2, 2009

And yeah, we haven't even gotten to tissue yet.
posted by muddgirl at 1:36 PM on December 2, 2009

Or maybe we have? I don't have any sound.
posted by muddgirl at 1:37 PM on December 2, 2009

I don't think I'm going to eat cold cuts for a while.

But regardless, fascinating stuff.
posted by Skygazer at 1:39 PM on December 2, 2009

I'm pretty sure they've hit brain. You can Jacopo scoop the slices off with the brush.
posted by Vhanudux at 1:39 PM on December 2, 2009

Is there sound?
posted by pearlybob at 1:40 PM on December 2, 2009

oooh drama! he's adding dry ice (or whatever that is)... again with bare hands?! Clearly not affecting his superskin.
posted by yiftach at 1:44 PM on December 2, 2009

No sound as far as I can determine, unfortunately, since he certainly seems to be doing a fair bit of 'splaining to folks... bummer.
posted by yiftach at 1:45 PM on December 2, 2009

This is unspeakably cool. If only I could get the local deli to slice my corned beef that thin.
posted by JeffK at 1:46 PM on December 2, 2009

Yeah, I didn't read the article till just now, and didn't realize that they're preserving the sections in that plastic box and are going to mount some of them later.
posted by muddgirl at 1:46 PM on December 2, 2009

Arrrrgghhh!!! I'm dying to know what he's saying!!
posted by pearlybob at 1:47 PM on December 2, 2009

We have brainsign!
posted by alexei at 1:48 PM on December 2, 2009

OK they just moved the camera and I'd advise squeamish people to avoid! I think it's really really cool, though!
posted by muddgirl at 1:48 PM on December 2, 2009

Whoa! Zooming in! I didn't think it could get cooler, and it it -- and more squicky for the squemish among us.
posted by natabat at 1:48 PM on December 2, 2009

I can see him pick up SOMETHING, Vhanudux, I'm just not sure it's brain tissue; I thought they were doing a cross section slice...

OH CRIMINY they just moved the camera into closeup -BRAAAIIIIIIINNNNSSSS!
posted by yiftach at 1:49 PM on December 2, 2009

Closeups!
posted by JeffK at 1:49 PM on December 2, 2009

I bet Jacopo gets the deli jokes all the time. But he does look like he could make a pretty tasty brain sammich. Which makes me think. Good thing there's no zombies in that laboratory right now. That would not be good.
posted by Skygazer at 1:49 PM on December 2, 2009

So what is the matrix in which the brain is suspended? Paraffin?
posted by JeffK at 1:52 PM on December 2, 2009

Gaaah. Why didn't I think to put the feed in another window earlier?

OK, neurogeeks: yes, there's tissue there. But Dr. Braincutter seems to be handling each slice rather cavalierly, even granting the large amount of ice that'll melt away shortly - isn't the brain getting all squished? Is it that easy to put back into shape?
posted by yiftach at 1:52 PM on December 2, 2009

I also love the they just thought to add large, readable labels to the microtome console so we know where we are in the process.

This. Is. Cool.
posted by yiftach at 1:54 PM on December 2, 2009

OK, neurogeeks: yes, there's tissue there. But Dr. Braincutter seems to be handling each slice rather cavalierly, even granting the large amount of ice that'll melt away shortly - isn't the brain getting all squished? Is it that easy to put back into shape?

Nah, the brain will be fixed, which means you can just sort of pick it up and let it do its thing. It'll go into some sort of cryoprotectant to stop it from getting cold damage and be fine. Even if it sticks to itself, the fixative (formalin or something similar) will mean it doesn't stay that way.
posted by gaspode at 2:00 PM on December 2, 2009

70 micron slices is pretty impressive, and definitely sounds extremely fragile. I remember seeing an entire sectioned human at the Chicago Field Museum (?) and it was both very impressive and very creepy at the same time; but those slices were at least a couple of millimeters thick or so, nothing like 70um. Combined with the ultra high resolution scans (200 DVDs worth of data per slice, whatever that means) this should result in a ton of data.
posted by Rhomboid at 2:03 PM on December 2, 2009

I don't think it's just in ice, but rather in some sort of polymer matrix, so while it might get softer as it warms up, it probably won't all melt away.

I may be a strange person for it, but man, this made my day.
posted by you're a kitty! at 2:09 PM on December 2, 2009

Imagine a whole wall covered with brain slices.
posted by Skygazer at 2:13 PM on December 2, 2009

This is really cool. For the record, people, it's not as gross as you think. The brain isn't bloody or anything because of the blood brain barrier and cytoplasm, and the way they're cutting into it, it's not like they're hacking at a loose brain with a chef's knife. It's in an opaque medium to hold it steady, and it's being cut by a very precise machine called a microtome.
posted by mccarty.tim at 2:24 PM on December 2, 2009

I, too, was worried about the brain getting all crinkled up, but I guess they know what they're doing.

You know what I find most impressive? Streaming flash video! Seriously, I clicked on the link and instantly got a very good quality live video feed from three camera angles. Yet why the hell do most sites offering any kind of streaming video insist on goddamn Quicktime or Windows Media rubbish that barely works.
posted by Jimbob at 2:32 PM on December 2, 2009

Neither the link to the live feed nor the one to the Brain Observatory website are working for me. And its killing me! I NEED TO SEE!! Does anyone have suggestions?
posted by bobobox at 3:04 PM on December 2, 2009

How many of you poked at the controls with your mouse? Be honest.
posted by CKmtl at 3:06 PM on December 2, 2009 [5 favorites]

bobobox: There's a mirror.
posted by natabat at 3:07 PM on December 2, 2009

Mirror of the video feed at the UCSD Neurosciences site.
posted by yiftach at 3:07 PM on December 2, 2009

Nice one, natabat.
posted by yiftach at 3:08 PM on December 2, 2009

How many of you poked at the controls with your mouse? Be honest.

I ... aw, fuck it. You got us figured out.
posted by Avenger at 3:11 PM on December 2, 2009

Imagine a whole wall covered with brain slices.

Further thought exercises -

Imagine a chair upholstered in brain slices.

Now, imagine a basketball net made of brain slices.

Finally, imagine a track suit with an interior lining of brain slices.
posted by FatherDagon at 3:11 PM on December 2, 2009

It looks like the brain is painted on the medium.

It's beautiful.
posted by yiftach at 3:15 PM on December 2, 2009

Thank you, natabat, yiftach.
This is excellent.
posted by bobobox at 3:16 PM on December 2, 2009

This is awesome!

Re: crinkling, according to this, the brain was first embedded in something more rigid, such as paraffin or epoxy. So the job is really to unfold the paraffin, rather then the brain itself. Still, it seems a tricky job not to tear a 70 µm thin slice, especially if you need to repeat the process 1500-2000 times!

What I'm wondering though, the brain is probably fixated using formalin to prevent cellular breakdown. This causes some of the structure to change, esp. membranes. How well does a fixated brain correspond with the real, in-vivo, thing?
posted by Zigurana at 3:27 PM on December 2, 2009

Gawd I love you guys. Reminds me of kids poking at dying worms. (NO, I did not watch video)
posted by Surfurrus at 3:30 PM on December 2, 2009

(NO, I did not watch video)

Seriously, I've seen a lot worse things in the freezer cabinet at my supermarket than in this video.
posted by Jimbob at 3:40 PM on December 2, 2009

At he project HM blog the fixation is explained:
"The brain has been embedded in 10% gelatin and the block was subsequently cross-linked in 4% Formaldehyde solution. Gelatin embedding is intended to provide support and adhesion for those tissue portions that would detach in thin cross sections of tissue."

In previous examination of the brain (using MRI), they found extensive white matter lesions, indicating severe demyelination of the white matter in the frontal lobes. Apart from being an issue of pathology, it also migh pose a problem when cutting these thin slices. The tissue is less firm in those places, and the gelatin cannot get there to provide support.
Ah, the stress, the excitement!
posted by Zigurana at 3:42 PM on December 2, 2009

They must be taking a smoke break right now.
posted by dead cousin ted at 3:43 PM on December 2, 2009

Finally, imagine a track suit with an interior lining of brain slices.
posted by FatherDagon at 6:11 PM on December 2 [+] [!]

How about a condom made of brain slices, or a raincoat or a shower curtain.

Hmm....all those devices hold back liquid. Don't know why I needed to make those all of-a-kind, especially as brain slices don't seem especially waterproof.
posted by Skygazer at 3:45 PM on December 2, 2009

These are single-serving slices, for zombies on a diet.
posted by gimonca at 3:53 PM on December 2, 2009 [3 favorites]

I can just barely make it out - it says Abby something-or-other.
posted by ooga_booga at 3:58 PM on December 2, 2009 [1 favorite]

Oh wait, it looks like they're taking a break. The sign looks like something you can buy at Hot Topic.
posted by ooga_booga at 4:00 PM on December 2, 2009

Took me a second to get that, but now I have a new t-shirt design!
posted by dead cousin ted at 4:07 PM on December 2, 2009

Oh wow, there's a kid there now. I think he belongs to the professor in the tan vest. Coolest dad (?) ever.
posted by mccarty.tim at 5:01 PM on December 2, 2009

What's the image resolution on these sections? I hope the dataset is going to be made available to the public, although distribution is going to be a issue. Maybe a down-sampled version can be shown on some kind of interactive browser.
posted by demiurge at 5:36 PM on December 2, 2009

Personally, I'm hoping they offer several different sizes of the data. Maybe a series of compressed JPEGs, as well as a full resolution torrent and 3D models made from the scans for people with the appropriate software.
posted by mccarty.tim at 5:50 PM on December 2, 2009

For the record, scientific organizations have distributed their stuff through bit torrent. Here's NASA sharing gigabyte-size PNGs of the Earth's surface each month. It's at a resolution of 1 pixel/500 meters, which kind of makes you realize how big the world is.
posted by mccarty.tim at 5:54 PM on December 2, 2009

Project H.M. Phase 2 Overview:
The main goals of Phase 2 are:
1. The exact cytological localization of the surgical lesion.
2. The application of histological staining using multiple markers to assess the pathological state of the brain.
3. The complete multimodal characterization of the case using multiple neuroimaging datasets, including: MRI, DTI, and blockface imaging in relation to images of microscopic anatomy acquired from selected giant histological sections. Whole giant tissue sections will be digitized at 20X and will be viewable within a dedicated web site. The web site will also enable shared consultation and annotation.


So the data will be partially available to the public, but no words about a download though. Bittorrent seems the way to (cheaply) distribute such large amount of data. Assuming 1500 slices, with an in-plane resolution of at least 0.1 mm, this will be a 3D volume consisting of roughly 1500x1500x1500 = 3.375^9 voxels. Stored as int16´s this would take up 2 byte per voxel, amounting to about 6GB. Not many people will have the hardware to scroll through such an immense dataset. A 3-D version of the multiscale googlemaps approach would be needed, especially for the web interface.
posted by Zigurana at 6:37 PM on December 2, 2009

It's going to be a hell of a lot more than 6 GB. The resolution is probably far finer than 0.1mm, for starters.

"Finally, the slides are ready to be digitized. Each is placed under a microscope at 20X magnification to distinguish individual cell types. A computerized camera next begins snapping pictures of the microscopic scene. It requires 20,000 such “capture tiles” to produce a mosaic of just one slide, enough digital information to fill 200 DVDs."

You guys really need to read the "what they hope to learn" link from the FPP. An excellent article.
posted by intermod at 7:35 PM on December 2, 2009

If you're shaving the brain, you're pressing too hard with your razor.
posted by Frank Grimes at 7:45 PM on December 2, 2009 [3 favorites]

You would have 3 bytes per voxel for the cryosections, 1 byte each for R, G, and B.

Even one microscopy slide is a heck of a lot of pixels. A viewer that I set up as a demo at work needs a zoomable image pyramid interface to show just one slide: javascript-based demo (not so fast), Silverlight-based demo (faster).

This article makes it seem like they're paying attention to the wrong part of the acquisition. They photo the top of the block, cut, and repeat. That part is fine, but then they talk about mounting the slides later and digitizing them. This is the wrong way to do it if you want a registered 3D reconstruction of the cryosections. The camera taking pictures on the top of the block can be registered and take pictures from the same position every time. The mounted slides will be stretched and ripped and won't be suitable for 3D reconstruction without a lot of image processing. Hopefully when their site is back up I can get the details.
posted by demiurge at 8:02 PM on December 2, 2009

It's going to be a hell of a lot more than 6 GB. The resolution is probably far finer than 0.1mm, for starters.

Here here. 6 gigs is nothin'. I wouldn't be surprised if the sort of Google Earthed Brain at least on the order of petabytes.

I would, however, be extremely surprised if that article is correct about 20X magnification though. I don't know what sort of conclusions they would draw about cytoarchitecture at that low a magnification.
posted by solipsophistocracy at 9:14 PM on December 2, 2009

intermod: You're right, that article is a great read, and it deserved more than my skimming over it.

demiurge: That demo looks great!

Its even more slices than I assumed, although they will mount not every one of them; "just" one in 30-50 slices. Still, this leaves between 50-100 slices to mount. Also, I learned that they do multiple stainings to highlight different cell structures, thus having the need for color images.

A heck of a lot of pixels indeed.

Fascinating post!
posted by Zigurana at 9:30 PM on December 2, 2009

"Please refresh regularly to view our current comments about where we are in the brain.

We are currently cutting the frontal lobe and listening to the Beatles' Let It Be.
Over 8,000 people are currently watching."

Another nice touch is that they provide a navigator map under the right bottom video.

(I don't know why I went to check this when working in lab this late at night normally left me in some state of sadness or madness, or doing faux karaoke and dancing around while doing experiments (a happy madness, i suppose.))

(using my pipettor as a mic no less)
posted by NikitaNikita at 9:49 PM on December 2, 2009

Metafilter: Shave Your Brain
posted by azpenguin at 11:34 PM on December 2, 2009

Speaking of brain slices, I heartily recommend this book.
posted by Skeptic at 1:37 AM on December 3, 2009

Someone should do a burma shave thing about this.
posted by Green With You at 8:36 AM on December 3, 2009 [1 favorite]

They had flown coach: Annese in the aisle seat, H.M.’s brain in a 19-quart white plastic cooler strapped next to him in the window seat.

Did the brain have to buy its own ticket? Could he have kept the cooler on his lap to save the extra fare?
posted by grapefruitmoon at 4:30 PM on December 3, 2009